CNS Tumors :

Gliomas
the most common group of primary brain tumors, they are tumors of the brain parenchyma that histologically resemble different types of glial cells

1- Astrocytomas 2- Oligodendrogliomas 3- Ependymomas

Several different categories of astrocytic tumors are recognized :
- On Macroscopic examination : - On Macroscopic examination :
1- Fibrillary Astrocytoma : They are infiltrative tumors that form : They are solid or papillary masses extending from the floor of the 4th ventricle.
- 80% of adult primary brain tumors, usually found in the cerebral hemispheres. - gelatinous, gray masses,
- may show cysts, focal hemorrhage, and calcification.
Fibrillary astrocytomas show a spectrum of histologic differentiation, based on the
degree of differentiation, they are classified into three groups:
- On microscopic examination:
1-astrocytoma, - On microscopic examination: The tumor is composed of :
2- anaplastic astrocytoma, - cells with regular, round to oval nuclei with abundant granular
3- glioblastoma . the tumor is composed of : chromatin.
- sheets of regular cells
- with spherical nuclei containing finely granular chromatin (similar to - Between the nuclei there is a variably dense fibrillary background.
- MORPHOLOGY : normal oligodendrocytes) surrounded by a clear halo of cytoplasm.

- The macroscopic appearance:

1- a poorly defined, infiltrative tumor that expands and distorts the invaded
brain
2- Some areas are firm and white, others are soft and yellow (the result of
tissue necrosis).
3- The cut surface of the tumor is either firm, or soft and gelatinous; cystic
degeneration may be seen.
4- In glioblastoma, there is a variation in the gross appearance of the
tumor from region to region.

- The microscopic appearance & grading : Tumor cells may form round or elongated structures (rosettes, canals) that
resemble the embryologic ependymal canal, with long, delicate processes extending
1- Astrocytoma: ( well-differentiated ) are characterized by : - The tumor contains a delicate network of anastomosing capillaries. into a lumen (Fig. 23-23B);
- mild to moderate increase in the number of glial cell nuclei - Calcification ranges from microscopic foci to massive depositions. more frequently present are perivascular pseudo-rosettes in which tumor cells
- nuclear pleomorphism, and an intervening feltwork of fine, GFAP- are arranged around vessels with an intervening zone consisting of thin ependymal
positive astrocytic cell processes that give the background a fibrillary - Mitotic activity is usually very difficult to detect. processes directed toward the wall of the vessel.
appearance.
- With increasing cell density, nuclear anaplasia, increased mitotic activity and With increasing cell density, nuclear anaplasia, increased mitotic activity and
- tumor cells can be seen infiltrating normal tissue at some distance from necrosis, the tumor becomes higher grade (anaplastic oligodendroglioma). necrosis, the tumor becomes higher grade (anaplastic ependymomas).
the main lesion.

2- Anaplastic astrocytomas ( moderately differentiated ) : Poorly Differentiated Neoplasms Other parenchyma tumors
- show regions that are more densely cellular and have greater nuclear
pleomorphism; with ncreased mitoses. - Medulloblastoma - Meningioma
The tumor is highly malignant. Meningiomas are benign tumors of adults, usually attached to the dura, arising from
3- glioblastoma ( poorly differentiated ) : the meningothelial cell of the arachnoid.
- On Macroscopic examination :
- The highest grade tumor, - On Macroscopic examination :
- it has a histologic appearance similar to anaplastic astrocytoma with the In children they are located in the midline of the cerebellum; in In adults
additional features of " lateral tumors occur more often. - Meningioma is attached to the dura with compression of underlying brain ,, my
extend to the overlying bone.
- necrosis and endothelial cell proliferation and pseudo- The tumor is often well circumscribed, gray, and friable, and may be seen extending
palisading nuclei.
to the surface of the cerebellar folia and involving the leptomeninges
- On microscopic examination:
- On microscopic examination:
2- Pilocytic Astrocytoma There are many different histologic patterns found in meningiomas, including:
They are extremely cellular, with sheets of anaplastic ("small blue") cells.
They are relatively benign tumors, often cystic, that occur in children and young 1- syncytial, clusters of cells sit in tight groups without visible cell membranes;
adults, and usually located in the cerebellum. Individual tumor cells are small, with little cytoplasm and hyperchromatic nuclei;
mitoses are abundant. 2- fibroblastic, with elongated cells and abundant collagen deposition between
- MORPHOLOGY : them;
- It is often cystic, with a mural nodule in the wall of the cyst; if solid, it
3- transitional, which shares features of the syncytial and fibroblastic types;
is usually well circumscribed.
- The tumor is composed of areas with bipolar cells with long, thin 4- psammomatous, with numerous psammoma bodies (Fig. 23-25B);
"hairlike" processes that are GFAP positive;
- Rosenthal fibers, eosinophilic granular bodies, and microcysts are often
present.
- Molecular genetics :
Certain genetic alterations is associated with the progression of infiltrating
astrocytomas from low to high grade
- Alterations most common in the low-grade astrocytomas are:
- mutations affecting p53
- overexpression of platelet-derived growth factor α (PDGF-A) and its receptor. 5- secretory, with PAS-positive intracytoplasmic droplets and intracellular
- The transition to higher grade astrocytoma is associated with: lumina by electron microscopy;

- disruption of two well-known tumor suppressor genes: RB --- 6- microcystic, with a loose, spongy appearance.
p16/CDKNaA --- tumor suppressor on chr. 19q.
(primary glioblastoma), - Atypical meningiomas
as new onset disease, occurs in older individuals lesions with a higher rate of recurrence, more aggressive local growth,

(secondary glioblastoma). - Anaplastic (malignant) meningiomas

younger patients with a past history of lower-grade astrocytoma. are highly aggressive tumors that resemble a high-grade sarcoma,

the molecular lesions found in the two types of glioblastoma tend to impinge on the
Metastatic Tumors
same pathways. For example: - Metastatic lesions, mostly carcinomas, account for approximately a quarter to half of intracranial tumors in hospital patients.
- The five most common primary sites are: lung, breast, skin (melanoma), kidney, and gastrointestinal tract,
1- Secondary glioblastomas usually have p53 mutations, WHILE
primary astrocytomas more commonly have amplification of MDM2, a gene that
encodes an inhibitor of p53. - MORPHOLOGY :
2- Similarly, while secondary glioblastomas have increased signaling through the
- Intraparenchymal metastases form sharply demarcated masses, often at the junction of gray matter and white matter,
PDGF-A receptor, WHILE primary glioblastomas often have amplified, mutated usually surrounded by a zone of edema.
epidermal growth factor receptor (EGFR) genes, which encode aberrant forms of - The boundary between tumor and brain parenchyma is well defined microscopically as well,
EGFR known as EGFRvIII.
- Nodules of tumor, often with central areas of necrosis, are surrounded by reactive gliosis.
Both types of mutations lead to increased receptor tyrosine kinase activity and the
activation of the RAS and PI-3 kinase pathways, which stimulate the growth and N.B. Meningeal carcinomatosis, with tumor nodules studding the surface of the brain, spinal cord, and intradural nerve roots, is
survival of tumor cells .
associated particularly with carcinoma of the lung and the breast.

Peripheral Nerve Sheath Tumors

1- Schwannoma These benign tumors arise from the neural crest–derived Schwann cell and cause symptoms by local
………………………………………………………compression of the involved nerve or adjacent structures (such as brainstem or spinal cord).
They are well-circumscribed, encapsulated masses that are attached to the nerve but can be separated from it .
On microscopic examination tumors show a mixture of two growth patterns :
1- In the Antoni A pattern of growth, elongated cells with cytoplasmic processes are arranged in
Morphology fascicles in areas of moderate to high cellularity and scant stromal matrix;
the “nuclear-free zones” of processes that lie between the regions of nuclear palisading are termed
Verocay bodies.
2- In the Antoni B pattern of growth, the tumor is less densely cellular and consists of a loose
meshwork of cells, microcysts and myxoid stroma.
In both areas the individual cells have an elongated shape and regular oval nuclei.
- A variety of degenerative changes may be found in schwannomas, including :
nuclear pleomorphism, xanthomatous change, and vascular hyalinization.
- Malignant change is extremely rare, but local recurrence can follow incomplete resection.
- Affected individuals often present with tinnitus and hearing loss;
Clinical pictrure - Sensory nerves within the dura are involved, including branches of the trigeminal nerve and dorsal roots.
- When extradural, schwannomas are most commonly found in association with large nerve trunks, where motor
and sensory modalities are intermixed.
2- Neurofibroma Neurofibromas can present as discrete localized masses—most commonly as a
(cutaneous neurofibroma) or in peripheral nerve as a (solitary neurofibroma) or as an infiltrative lesion growing within and
expanding a peripheral nerve (plexiform neurofibroma).
a- Cutaneous Neurofibroma :
- these well-defined but unencapsulated masses are composed of spindle cells.
- they are not invasive,
- The stroma of these tumors is highly collagenized and contains little myxoid material.
- Lesions within peripheral nerves are of identical histologic appearance.
b- Plexiform Neurofibroma :
(These tumors may arise anywhere along a nerve)
The affected nerves are irregularly expanded, and unlike schwannomas, it is not possible to separate the lesion
from the nerve.
On microscopic examination,
- the lesion has a loose, myxoid background with a low cellularity.
- Several cell types are present, including Schwann cells, larger multipolar fibroblastic cells, and
….inflammatory cells, including mast cells.
- Although the myxoid stroma dominates, there are often areas of collagen bundles, which have a “shredded
…carrot” appearance.
- The risk of malignant transformation of these tumors is extremely small,
- In contrast, plexiform tumors may result in significant neurologic deficits when they involve major nerve trunks,
are difficult to remove because of their intraneural spread, and have a significant potential for malignant
transformation.